Pheochromocytoma cells in vitro may show morphological and functional properties of classic neurons and of classic endocrine cells. "Neural" properties include neurite-like processes and small vesicles, choline acetyltransferase, specific antigens and sodium action potential channels. "Endocrine" properties include large "chromaffin" granules and peptide hormones. It is not clear to what extent ability to express these properties reflects normal pluripotency of "neuroendocrine programmed" cells, and to what extent it is a manifestation of neoplasia. Background studies indicate that nerve growth factor (NGF) may cause pheochromocytoma cells to cease dividing and acquire morphological and functional characteristics of neurons, and also suggest that normal chromaffin cells remain responsive to NGF in adult life. Normal and neoplastic chromaffin cells may also be influenced by epidermal growth factor (EGF) and corticosteroids. The proposed study will seek to identify interactions between NGF, EGF and steroid hormones which regulate "neural" and endocrine" phenotypic markers and cell division in neoplastic, hyperplastic and normal adrenal chromaffin cells in culture, and to determine whether specific responses to these agents or to culture conditions may be correlated with neoplastic progression. The molecular level at which these agents exert their effects will be investigated by use of inhibition of transcription, translationa and replication. The role of cell-substratum adhesion in initiating or modulating effects of NGF and EGF will be studied by comparing effects of these growth factors in spinner and monolayer cultures. Mechanisms for storage and release of peptide hormones by chromaffin cells will be compared to known mechanisms for catecholamines. It is hoped that these studies will clarify events which determine normal neuroendocrine cell phenotype, and which are involved in the pathogenesis of neuroendocrine neoplasia.